05_Morphogenesis_Q and A_Jonathan Flashcards Preview

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Flashcards in 05_Morphogenesis_Q and A_Jonathan Deck (45):
1

Q and A are done from the lecture. There may be some details in the notes that are not covered here. (see morphogenesis notes 2)

Q and A are done from the lecture. There may be some details in the notes that are not covered here. (see morphogenesis notes 2)

2

Define Basal plate

The ventral part of the neural tube that becomes the motor part of the nervous system.

3

Define Alar plate

The dorsal part of the neural tube that becomes the sensory part of the nervous system.

4

Define Floorplate

The ventralmost part of the neural tube.

5

Define Notocord

The embryonic structure immediately ventral to the neural tube.

6

Define BMP (Bone Morphogenic Protein)

Ectoderm manufactures this and its effect must be blocked in order to allow the neural tube to form. Also, once the neural tube is formed, it promotes development of the dorsal aspect of the neural tube.

7

Define TGF-β (transforming growth factor)

A family of compounds, including BMP, retinoic acid and dorsalin, that promote development of the dorsal side of the neural tube.

8

Define Noggin & chordin

Secreted by the basal plate and notocord. These inhibit BMP to allow the neural tube to form and also promote the development of the basal plate of the neural tube.

9

Define Notch & Numb

Numb antagonizes notch effect on gene transcription. As long as notch is suppressed, the cell keeps replicating. When notch dominates, the cell stops dividing.

10

Define Notch & Delta

Delta, expressed on a cell surface interacts with notch on the adjacent cell, which inhibits delta expression in that cell. This results in adjacent cells having high levels of notch and delta. High notch results in a glioblast, high delta results in a neuroblast. Therefore, glia and neurons are intermixed.

11

Define Basic helix-loop-helix genes (bHLH)

Activation of these genes contributes to development of a neuron.

12

Neural Crest Cells become neuronal and non-neuronal cells.
What are some examples of neuronal cells?
What are some features of these cells?

• Dorsal root (spinal) ganglia and all sensory nerve fibers
• Ganglia of cranial nerves
• Autonomic ganglia, including in the gut

• Adrenal medulla
• All elements of the PNS except somatic and preganglionic autonomic motor axons

13

Neural Crest Cells become neuronal and non-neuronal cells.
What are some examples of non-neuronal cells?

• Schwann cells and satellite cells
• Leptomeninges (pia/arachnoid)
• Bone and connective tissues of the face and most of the skull

14

Describe the formation of the neural tube.

• 18 days from conception
• Ectoderm produces Bone Morphogenic Protein that blocks the development of the neural tube
o BMP is in the TGF-beta family
• Notochord secretes Noggin, Chordin, and Follistatin that inhibit BMP
• Ectoderm ==> neural epithelium over the notochord ==> neural groove
• Day 20 ==> neural groove zips up from center to cephalic and caudal

15

What does the neural tube and its hollow space become?

• The hollow tube becomes the ventricular system and the walls become the brain and the spinal cord

16

What are the factors that differentiate the ventral from dorsal part of the neural tube?

• Ventral: sonic hedgehog
o Don’t need to know: also, retinoic acid, noggin, and chordin
• Dorsal: TGF-B family: BMP
o Don’t need to know: also, dorsalin, retinoic acid, noggin
• Note: same signals can do different things at different times and different concentrations

17

Notochord ==> sonic hedgehog ==> induces ventral neural tube ==> basal floor plate ==> then the basal floor plate secretes compounds

Notochord ==> sonic hedgehog ==> induces ventral neural tube ==> basal floor plate ==> then the basal floor plate secretes compounds

18

Sonic Hedgehog (Shh) is both necessary and sufficient (?) to induce the ventral dorsal axis in the neural tube. As a diffusible molecule, its concentration also induces middle neural tube cells

Sonic Hedgehog (Shh) is both necessary and sufficient (?) to induce the ventral dorsal axis in the neural tube. As a diffusible molecule, its concentration also induces middle neural tube cells

19

How can statins be teratogenic?

• Shh is inactive when released and undergoes autoproteolysis
• Amino-terminal fragment contains signaling functions
• The fragment must bind to cholesterol, which is required for proper diffusion and activity
• Statins can lower cholesterol and injure the developing fetus

20

What is Patched (PTC)? What are Smoothened (SMO)? What is their significance in neural development?

• PTC is a Shh receptor
• PTC normally inhibits Smoothened (SMO)
• When Shh binds to PTC, SMO is released
• SMO activates several transcription factors necessary for the ventral-dorsal neural tube development

21

What is the sulcus limitans?

• It is the space where the basal and alar plates meet near the hollow part of the neural tube (slide 24)
• Note the hollow part of the neural tube is now lined with ependyma

22


Where are the following found within the neural tube…
Somatic motor neurons?
Sensory neurons?
Visceral motor and sensory neurons?

• Somatic motor neurons are most ventral (basal plate)
• sensory neurons are most dorsal (alar plate)
• visceral motor and sensory nuclei (i.e., autonomic) are closest to sulcus limitans.

23

What happens to the alar plate and the basal plate at the brainstem? What nervous system structure is formed? (see slide 25 for cartoon)

• the dorsal neural tube splays outward such that the left and right alar plates separate and become lateral ventral.
• The left and right basal plates remain together and become medial ventral
• The space created by the splay is the fourth ventricle

24

In the brainstem, Cranial nerve nuclei with similar functions are distributed longitudinally in the brain stem (motor medial; sensory lateral). Motor nuclei to pharyngeal arch muscles are displaced ventrally

In the brainstem, Cranial nerve nuclei with similar functions are distributed longitudinally in the brain stem (motor medial; sensory lateral). Motor nuclei to pharyngeal arch muscles are displaced ventrally

25

What is Holoprosencephaly?

• Shh deficiency

26

Note: there are other inducing growth factors at work in the neural tube. We do not need to know these specifically.

Note: there are other inducing growth factors at work in the neural tube. We do not need to know these specifically.

27

What are the primary vesicles?

• caudal to rostral: Rhombencephalon ==> Mesencephalon ==> Prosencephalon

28

Where is the cervical flexure and the cephalic flexure?

• Cervical flexure is at the rhombencelphalon
• Cephalic flexure is at the mesncephalon

29

Describe the development of the primary vesicles ==> secondary vesicles. See slide 29 or page 4 of the notes

• At the pontine flexure, the rhombencephalon ==> divides into the myencephalic vesicle and the metencephalic vesicle
• myelencephalon ==> the caudal part of the 4th ventricle, i.e., the medulla
• metencephalic vesicle ==> the metencephalon becomes the rostral part of the 4th ventricle, i.e., the pons.
• Rostrally, prosencephalic vesicle ==> develops a midline vesicle and the lateral outpouchings
• Midline vesicle ==> the diencephalic vesicle, that becomes the third ventricle
• Lateral outpouchings ==> the telencephalic vesicles, which develop into the lateral ventricles

30

What causes the Rostral-Caudal organization of the spinal cord and brain?

• diffusible compounds that effect transcription factors
• Retinoic acid concentrated in the cervical area produces a gradient that activates TFs
• Hox genes
• High concentration of Vitamin A ==> caudal signal
• Low concentration of Vitamin A ==> rostral signal

31

What is a Rhombomere?

• a transiently divided segment of the developing neural tube, within the hindbrain region (a neuromere) in the area that will eventually become the rhombencephalon.
• The rhombomeres appear as a series of slightly constricted swellings in the neural tube, caudal to the cephalic flexure.
• present by day 29.

32

Why is Vitamin A a Teratogen?

• Vitamin A concentration within each Rhombomere tells it to develop into its given function.
• We could disrupt if concentration of vitamin A in incorrect place.

33

Explain the process of dividing precursor cells in the vertebrate neuroepithelium. (slide 33). What is this area of proliferation called?

• one cell spans the neuroepithelium form the neural tube to the pia mater.
• The cell nucleus travels back and forth.
• At the pia side, it doubles its DNA
• At the neural tube side it divides by mitosis
• Note: These cells undergo massive proliferate and go on to become neural, glial, or ependymal cells. This area of proliferation is called the ventricular zone.

34

Note: Notch and Numb are found within neuroepithelial cells at the neural tube.

Note: Notch and Numb are found within neuroepithelial cells at the neural tube.

35

What are the effects of Notch & Numb?

• Numb antagonizes notch effect on gene transcription.
• As long as notch is suppressed, the cell keeps replicating.
• When notch dominates, the cell stops dividing and starts migrating

36

Explain the division of cells with regard to Notch and Numb.

• Notch and Numb are both found within a cell
• Notch is on the rostral side. Numb is on the caudal side. (?)
• If the cell divides along a vertical axis, the two daughter cells each receive an even amount of notch and numb.
• If the cell divides along a horizontal axis, one cell has an excess of Notch. Another cell has an excess of Numb.

37

Notch Details (don’t need to know):

Notch is an integral membrane protein that functions as receptor for ligands such as jagged and delta that are associated with the surface of neighboring cells. Upon ligand binding, notch is proteolytically cleaved within its transmembrane domain by presenilin-1 (the enzymatic component of the gamma-secretase complex) resulting in the release of a notch intracellular domain which translocates to the nucleus where it regulates gene expression. Notch signaling plays multiple roles in the development of the CNS including regulating neural stem cell (NSC) proliferation, survival, self-renewal and differentiation. Notch is also present in post-mitotic neurons in the adult CNS wherein its activation influences structural and functional plasticity including processes involved in learning and memory.

38

What are factors that determine whether a cell will become a neuron or a glial cell? What determines when a cell becomes a ependymal cell?

• Notch on one cell interacts with Delta on an adjacent cell
• Delta plus Basic Helix-Loop-Helix genes cause cells to develop into neuroblasts
• Notch causes its own cell to develop into a glial cell (astrocytes, oligodendrocytes, etc)
• Note: this creates alteration between neural and glial cells (eventually, neural cells commit apoptosis, so we end up with 10x more glial cells)
• Cells that escape those two fates go on to become ependymal cells

39

What are the three layers of the developing neural tube (center to periphery)?

• Ventricular zone
• Mantel zone (basal and alar plate)
• Marginal zone (white matter)

40

How do neurons migrate from the ventricle to the brain?

• Neurons migrate along radial glia that maintain a connection from the ventricular zone to the surface of the brain until cells reach their place signaled by some attractive surface (contact factors)
• Neurons travel to the mantle or the marginal zone.

41

What do the ventricular, mantle, and marginal zones become?

• ventricular ==> ependymal cells
• mantle ==> most of the substance of the spinal cord and brain.
o As axons begin to move out from the cells, they enter the periphery of the tube, comprising the marginal zone.
o The spinal cord maintains these layers.

42

Explain the development of the layers of brain in the cerebral cortex.
See slides 42-46

• Radial glial cells maintain connections to the very surface of the cerebral cortex for a long time (this surface layer becomes cortical layer I).
• Then there are 5 waves of neuronal migrations into the cerebral cortex (representing cortical layers II-VI).
• Each wave migrates though the prior set of neurons until they bump up against cortical layer I.
• This means that the oldest layer of the cortex is layer I, but the next oldest (developmentally) is layer VI.
• Migration continues for quite some time and is subject to being disrupted.
o Radial glial cells that are misformed cause extensive damage: ectopic cortex

43

What are Cajal-Retzius cells?

• The term Cajal–Retzius cell is applied to reelin-producing neurons of the human embryonic marginal zone that display, as a salient feature, radial ascending processes that contact the pial surface and a horizontal axon plexus located in the deep marginal zone.
• Cajal-Retzius cells release reelin (spatial signal) to guide migration of neurons to cortex.

44

Inhibitory cells migrate in from the ventral side

Inhibitory cells migrate in from the ventral side

45

What causes cells that migrate to become their final cell type?

• cells that migrate are affected by the mileu of chemical signals from the cells that they migrate through
• Cell fate is determined by those signals